rs317807

Variant names:

• chr18-57583438-G-A
• rs317807
• NM_000140.5:c.67+3116C>T

Your query was ambiguous. Multiple possible variants found:

• chr18-57583438-G-A
• chr18-57583438-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000140.5(FECH):​c.67+3116C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,174 control chromosomes in the GnomAD database, including 6,142 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (6142 hom., cov: 33)
• Consequence: FECH NM_000140.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.538
• Publications: 8 publications found

Genes affected

FECH (HGNC:3647): (ferrochelatase) The protein encoded by this gene is localized to the mitochondrion, where it catalyzes the insertion of the ferrous form of iron into protoporphyrin IX in the heme synthesis pathway. Mutations in this gene are associated with erythropoietic protoporphyria. Two transcript variants encoding different isoforms have been found for this gene. A pseudogene of this gene is found on chromosome 3.[provided by RefSeq, May 2010]

FECH Gene-Disease associations (from GenCC):

• protoporphyria, erythropoietic, 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Laboratory for Molecular Medicine, ClinGen, Labcorp Genetics (formerly Invitae)
• autosomal erythropoietic protoporphyria

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FECH	NM_000140.5	c.67+3116C>T		intron_variant	Intron 1 of 10	ENST00000262093.11	NP_000131.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FECH	ENST00000262093.11	c.67+3116C>T		intron_variant	Intron 1 of 10	1	NM_000140.5	ENSP00000262093.6

Frequencies

GnomAD3 genomes AF: 0.263 AC: 40008 AN: 152056 Hom.: 6142 Cov.: 33

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.291

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.263 AC: 40013 AN: 152174 Hom.: 6142 Cov.: 33 AF XY: 0.267 AC XY: 19848 AN XY: 74388

African (AFR) AF: 0.138 AC: 5725 AN: 41546

American (AMR) AF: 0.271 AC: 4142 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1081 AN: 3472

East Asian (EAS) AF: 0.641 AC: 3320 AN: 5176

South Asian (SAS) AF: 0.406 AC: 1960 AN: 4822

European-Finnish (FIN) AF: 0.268 AC: 2839 AN: 10578

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.292 AC: 19844 AN: 67990

Other (OTH) AF: 0.294 AC: 621 AN: 2110

Alfa AF: 0.283 Hom.: 8906

Bravo AF: 0.259

Asia WGS AF: 0.486 AC: 1686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.4
DANN	Benign	0.64
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs317807; hg19: chr18-55250670;